When the FDA halted all clinical work with Protagonist's rusfertide over cancer concerns, investors feared the worst. The lifting of that hold a mere three weeks later therefore prompted a similarly dramatic reaction: the stock surged 94% yesterday. But the shares still sit some 25% below levels seen before the clinical hold. Aside from requiring enhanced monitoring for skin cancer, the FDA seems comfortable for the programme to continue largely as before. Such a swift resolution is reassuring, though confidence in rusfertide’s potential has clearly taken a knock. More data will help, and two presentations before year end are now keenly awaited. The first is at the Liver Meeting, concerning a second indication for the project: hereditary haemochromatosis, a rare inherited disorder that causes iron build-up. Phlebotomy is the effective but burdensome standard of care. The abstract points to a dramatic reduction in phlebotomies as well as improvements in various pharmacological markers. The latest cut from an ongoing phase 2 trial in polycythemia vera is also due, possibly at Ash. Protagoinst confirmed yesterday that it still plans to start phase 3 in polycythemia vera early next year.  

Astrazeneca is already seeking authorisation of its antibody combo AZD7442 for the prevention of Covid-19. Today’s topline data from the Tackle study show the project to have utility in the outpatient treatment setting, too, halving the risk of severe infection or death when given within seven days of symptom onset. In a prespecified subset who received the treatment within five days of symptom onset, AZD7442 cut this risk by 67% versus placebo. But there are a couple of reasons for caution. Most obviously, Merck & Co recently showed a similar level of efficacy in the same setting with molnupiravir, which has the vast advantage of being oral. And several other antibodies and antibody combos are already authorised for the treatment of non-hospitalised patients, with notably better headline efficacy than AZD7442. Perhaps ’7442 has a bit of an edge over these in that it is long-acting, and is delivered intramuscularly rather than needing to be infused – but molnupiravir clearly still wins on convenience. Forecast sales for ’7442 are far behind the blockbuster numbers the sellside has pencilled in for many of these treatments, and this situation seems unlikely to change on the back of the Tackle data. 

Chemocentryx finally got the green light today for Tavneos in ANCA-associated vasculitis after a Pdufa delay, and the thumbs up follows previous precedent in that Pdufa date extensions rarely result in knockbacks. While the news sent Chemocentry’x shares soaring 64% the reaction is still not enough to put the company to levels seen before the mixed adcom in May, when shares lost three quarters of their value. The FDA’s concerns over liver toxicity seem to have been abated with the use of frequent liver function tests, and Tavneos's label comes without a black box warning. Tavneos, a complement C5a inhibitor, has been pegged as a pipeline in a product, but has suffered mid-stage setbacks in hidradenitis suppurativa and glomerulonephritis, thus leaving vasculitis as its main source of revenue.

Why deucravacitinib would fail in ulcerative colitis when it succeeded convincingly in psoriasis is not clear, but fail it has. In the phase 2 Lattice-UC study Bristol Myers Squibb’s oral Tyk2 inhibitor did not show improved clinical remission over placebo in moderate to severe UC. Neither did the trial meet its secondary efficacy endpoints. Deucravacitinib might still have a chance in the condition: a second phase 2 trial testing a higher dose is under way, and could report imminently. But hopes in UC will surely dim, not least because Pfizer has already discontinued its Tyk2, PF-06826647, in the disease. Perhaps deucravacitinib is a better bet in the various other disorders in which it is being trialled, though for now psoriasis remains the only indication for which analysts are forecasting sales – $2.4bn in 2026, according to Evaluate Pharma. The news will hardly help shore up confidence in Bristol’s biggest pipeline hope, which has already been dented by regulatory concerns. The company’s shares have slid heavily since the FDA slapped surprisingly stringent warnings on the related Jak-inhibitor class, with investors fearful that the regulator might consider the Tyk2 mechanism to carry similar risks.

Boston Scientific’s management has spoken in doom-laden tones of the effect Delta variant Covid-19 is having on elective procedures, and has hinted to analysts that it might not meet its third-quarter sales growth forecast of 12-14% as a result. Its acquisition of the Canadian group Baylis Medical Company for $1.75bn cash today is therefore a way of guarding against, or at least making up for, a revenue shortfall. Baylis is squarely in Boston’s cardiovascular wheelhouse as a manufacturer of minimally invasive products to aid in procedures like cardiac ablation, left atrial appendage closure and mitral valve intervention. It is growing at double-digit rates, Boston says, and is expected to generate revenues approaching $200m next year. The purchase of Baylis is Boston’s third $1bn-plus deal this year – notable given that the group has only done nine such deals in the past quarter century. And more might be on the way; Boston has repeatedly stated its intention of growing through acquisitions. At the end of June Boston had $2.7bn cash on hand, and investors might now be starting to wonder how deep its pockets are. 

Astrazeneca’s filing for emergency use of AZD7442 for Covid-19 prevention looks like an attempt to steal a march on Regeneron and Lilly’s already authorised MAbs. Whether it will succeed is a separate question. Astra says “AZD7442 (could) be the first long-acting MAb to receive an EUA for Covid-19 prevention”, though Regeneron’s Regen-Cov and Lilly’s bamlanivimab/etesevimab, both normal-acting, already have EUAs for post-exposure prophylaxis in subjects at high risk of severe Covid-19. Astra’s application appears to seek a broad EUA for Covid-19 prevention, even though only its pre-exposure study, Provent, succeeded; Storm Chaser, for post-exposure prophylaxis, failed. A separate question for the FDA will be whether to authorise AZD7442 in vaccinated as well as unvaccinated people; the Regeneron and Lilly prophylaxis EUAs are for unvaccinated people and those who are vaccinated but unable to mount a strong immune response, but Astra’s trials were specifically in the unvaccinated population. A similar consideration exists for Merck & Co’s oral antiviral molnupiravir, which last week scored in a Covid-19 treatment study in unvaccinated people. While it might seem unethical to deny a drug based on patients’ vaccination status, reimbursement for molnupiravir might be justifiable only in its specific studied population.

Microbiome-targeting agents seem to have a decent shot at treating C difficile infections, if they are rather less certain in other settings. Vedanta said today that its pill VE303, a combination of eight strains of live bacteria grown in cell banks, achieved a 31.7 percentage point risk reduction versus placebo in the rate of infection recurrence. The data refer to only the higher dose administered in the phase 2 Consortium trial; on the lower dose Vedanta is silent. Still, the data were good enough to spur Barda to hand over $23.8m to support phase 3 studies, under a contract it has had with Vedanta since last year. These trials ought to begin next year, putting Vedanta some way behind Seres and Ferring. The former hopes to file its C diff project SER-109 for US approval next year, and Ferring should get its pivotal data in the same time frame. Elsewhere, Kaleido Biosciences reported topline biomarker data from a tiny trial of its microbiome asset KB295 in mild-to-moderate ulcerative colitis. A phase 2 trial is slated for 2022, and the group will hope to avoid the dismal fate of Seres in this disease. 

The medtech Spac scene seems to be going through one of its periodic lulls, with just one deal announced in August and one in September. The latter is the acquisition of Prenetics, a genomics and diagnostics testing company based in Hong Kong, by the Nasdaq-listed Artisan Acquisition Corp. The deal values Prenetics at around $1.3bn, not unreasonable considering its forecast 2021 revenues of $205m. Once public the group, whose claim to fame is supplying the Covid-19 tests used by the UK’s Premier League, has ambitions to expand into the US via M&A. Looking at the other end of the Spac process, seven companies have closed their deals and now enjoy stock market listings. But their performance has been decidedly mixed. Vicarious Surgical’s 50% rise reflects the high hopes for new entrants into the fast growing robotic surgical space, whereas the baby-monitoring tech company Owlet crashed 26% on August 25 when several of its backers, including its Spac’s sponsor, Sandbridge Capital, registered to sell their shares. 

Seven years after floating Xenon could finally have found a winner. Highly encouraging data from the phase 2b X-Tole trial of XEN1101 sent shares in the company to a record high. The study tested the Kv7 potassium channel modulator in adults with focal epilepsy; XEN1101 significantly reduced seizure frequency versus placebo across three doses, and hit secondary measures. This was a highly refractory patient group that had failed a median of six previous anti-seizure medications; half remained on three background ASMs. On a call Xenon executives said it was highly unlikely to win approval on this trial alone, but hoped that regulators would accept X-Tole as one of two required studies. Safety also looked encouraging, with no suggestion that XEN1101 was worsening mood; many ASMs have a black box warning of suicidal ideation. Stifel analysts said the data beat expectations and looked in line with the recently approved Xcopri. To put a value on the opportunity, Angelini agreed to pay almost $1bn earlier this year for Arvelle, owner of Xcopri's European rights. Analysts expect Xcopri's sales in the US, where it is sold by SK Biopharmaceuticals, to reach $846m by 2026, according to Evaluate Pharma.

While there were FDA setbacks for Calliditas and Verrica last month there were also a couple of early oncology approvals. One such win was for Tivdak, Seagen/Genmab’s treatment for recurrent or metastatic cervical cancer. However, expected sales of Tivdak could be hit by an unexpected black box warning regarding ocular toxicity. An early approval for Takeda’s Exkivity also came with safety implications. The oral therapy, used to treat lung cancer driven by EGFR exon 20 insertions, has a black box warning for QTc prolongation. J&J’s competing project Rybrevant does not come with a warning, but is less convenient as it is an infused antibody. Separately, Takeda investors are still holding out for FDA news on Eohilia after the FDA's action date was missed in April. Takeda says Eohilia could become the first treatment for eosinophilia oesophagitis, but with a filing for Sanofi/Regeneron’s Dupixent expected next year Takeda will want the regulators to hurry.